PROJECT SUMMARY Sub-Saharan Africa (sSA) is home to the fastest growing and youngest population in the world and includes countries with the highest HIV prevalence globally. More than half of sSA's population is under 25 years of age. Men and women aged 10-24, defined as `young people' by the United Nations Population Fund (UNFPA), represent one third of the sSA population and this proportion continues to grow. Young women in sSA who are economically and educationally disadvantaged are at high risk of engaging in transactional sex. Sex workers under 16, new to sex work are much more vulnerable than their older colleagues to violence, STIs and HIV. As sex work is illegal in Uganda, this contributes to the risk these young women face. Effective STI and HIV prevention, care, support, and reproductive health services are critical. Evidence on interventions that address uptake and adherence to HIV prevention services for high-risk populations is limited, but interventions that address YWHR are almost non-existent. In response to RFA-MH-17-560, we are proposing a R34 to develop a comprehensive intervention including PrEP and HIV self-testing for HIV-uninfected women 15- to 24-years old who engage in high-risk sexual activity in Kampala, Uganda, and conduct a pilot trial to evaluate its feasibility, acceptability and potential effect on PrEP uptake and adherence as well as repeat HIV self-testing. We will embed this study within our existing cohort study (NIMH R01 HD085805-01, PI King) that has revealed the need for greater attention to young sex workers soon after their initiation into the profession given early results in our mobilization efforts that have shown much higher HIV prevalence than expected. The intervention will focus on increasing initiation of PrEP with enhanced adherence support, uptake of repeat HIV testing by self- test, and motivation to adopt and sustain sexual risk reduction behaviors for STI, HIV, and unplanned pregnancy. The specific aims are (1) To conduct formative research to enhance our understanding of the dynamics of the social and sexual networks, and context of women (aged 15-24) engaged in high risk sexual behavior in Kampala, Uganda and barriers and opportunities for PrEP uptake and adherence as well as repeat HIV testing by self test; (2) To develop and test a socially and culturally acceptable and feasible prevention intervention on uptake and adherence to PrEP and HIV self-testing for young women at high risk for HIV; (3) to translate lessons learned in the pilot study into the design of a larger RCT. The proposed project is responsive to several priority areas of the President's Emergency Plan for AIDS Relief and the World Health Organization regarding HIV prevention among young people. Our proposal represents one of the first studies to develop an integrated bio-behavioral-structural approach to HIV prevention among young women at high risk in resource- limited settings.